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The gastrointestinal tract plays a role in the development and treatment of metabolic diseases. During a meal, the gut provides crucial information to the brain regarding incoming nutrients to allow proper maintenance of energy and glucose homeostasis. This gut–brain communication is regulated by various peptides or hormones that are secreted from the gut in response to nutrients; these signaling molecules can enter the circulation and act directly on the brain, or they can act indirectly via paracrine action on local vagal and spinal afferent neurons that innervate the gut. In addition, the enteric nervous system can act as a relay from the gut to the brain. The current review will outline the different gut–brain signaling mechanisms that contribute to metabolic homeostasis, highlighting the recent advances in understanding these complex hormonal and neural pathways. Furthermore, the impact of the gut microbiota on various components of the gut–brain axis that regulates energy and glucose homeostasis will be discussed. A better understanding of the gut–brain axis and its complex relationship with the gut microbiome is crucial for the development of successful pharmacological therapies to combat obesity and diabetes.

The gastrointestinal tract plays a role in the development and treatment of metabolic diseases. During a meal, the gut provides crucial information to the brain regarding incoming nutrients to allow proper maintenance of energy and glucose homeostasis. This gut-brain communication is regulated by various peptides or hormones that are secreted from the gut in response to nutrients; these signaling molecules can enter the circulation and act directly on the brain, or they can act indirectly via paracrine action on local vagal and spinal afferent neurons that innervate the gut. In addition, the enteric nervous system can act as a relay from the gut to the brain. The current review will outline the different gut-brain signaling mechanisms that contribute to metabolic homeostasis, highlighting the recent advances in understanding these complex hormonal and neural pathways. Furthermore, the impact of the gut microbiota on various components of the gut-brain axis that regulates energy and glucose homeostasis will be discussed. A better understanding of the gut-brain axis and its complex relationship with the gut microbiome is crucial for the development of successful pharmacological therapies to combat obesity and diabetes.

Diaphragmatic function is important in treating respiratory failure. Muscle endurance has been measured using twitch electrical stimulation and accelerometer-based mechanomyography. The purpose of this study was to evaluate the reproducibility and the time to perform an endurance test on the diaphragm muscle using electrical stimulation of the phrenic nerve. Twenty healthy subjects (21.6±1.6yrs) were tested in the supine position on two separate occasions. Stimulation electrodes were placed on the left (n=18) or right (n=2) phrenic nerve underneath the sternocleidomastoid muscle. A tri-axial accelerometer was placed on the abdomen and 5 minutes of submaximal electrical stimulation at 5Hz was performed. The resultant vector of acceleration at peak and end acceleration was analyzed: endurance index = end/peak*100). The test was successfully completed 41/47 times. The endurance index for the two days was 73.8±9.4% and 72.6±11.1%, respectively. The time to find the phrenic nerve was 34.8±13.1s for the first 10 subjects and 13.0±2.8s for the second 10 subjects. For the second group, the mean difference in endurance between days was 0.03% with a 95% confidence interval of -1.6% to 1.5%. In conclusion, the diaphragm endurance test was reproducible with practice.

BACKGROUND: Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. METHODS: We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (

Background Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web‐based data collection system for early‐stage MF with legal data‐sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in‐built intelligence in the database system ensures accurate staging. Objectives To develop a prognostic index for MF. Methods Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. Results In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early‐stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 1290)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. Conclusions This confirmed early‐stage MF cohort is being followed‐up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.

Summary Background Bexarotene is a synthetic retinoid from the subclass of retinoids called rexinoids which selectively activate retinoid X receptors. It has activity in cutaneous T-cell lymphoma (CTCL) and has been approved by the European Medicines Agency since 1999 for treatment of the skin manifestations of advanced-stage (IIB–IVB) CTCL in adult patients refractory to at least one systemic treatment. In vivo bexarotene produces primary hypothyroidism which may be managed with thyroxine replacement. It also affects lipid metabolism, typically resulting in raised triglycerides, which requires prophylactic lipid-modification therapy. Effects on neutrophils, glucose and liver function may also occur. These side-effects are dose dependent and may be controlled with corrective therapy or dose adjustments. Objectives To produce a U.K. statement outlining a bexarotene dosing schedule and monitoring protocol to enable bexarotene prescribers to deliver bexarotene safely for optimal effect. Methods Leaders from U.K. supraregional centres produced this consensus statement after a series of meetings and a review of the literature. Results The statement outlines a bexarotene dosing schedule and monitoring protocol. This gives instructions on monitoring and treating thyroid, lipid, liver, blood count, creatine kinase, glucose and amylase abnormalities. The statement also includes algorithms for a bexarotene protocol and lipid management, which may be used in the clinical setting. Conclusion Clinical prescribing of bexarotene for patients with CTCL requires careful monitoring to allow safe administration of bexarotene at the optimal dose.

Herein, the Georadiological Barrier Gamma Attenuation Model that is developed in Part 1 of this paper, is utilized to estimate the attenuation of gamma (γ) rays by earthen barriers of various thicknesses and material composition. Activities of radioactive isotopes are calculated and coupled with an exponential absorption equation, to estimate γ exit intensities from these georad barriers. The results indicate that γ attenuation by georad barriers is more significantly affected by barrier thickness than by barrier density. A 33% increase in thickness from 15 to 20 cm produces a 50% reduction in emitted γ intensity, while a 33% increase in density from 1.5 to 2.0 g∕ cm3 produces a 19% reduction for a barrier comprising 45% sand, 25% clay, and 30% water (by weight). This model can be used to optimize barrier material mix composition, density, and thickness to increase γ attenuation in emergency response at existing radiologically contaminated sites and during response scenarios.

Containment systems for surface soils that are contaminated with radioactive substances must provide emissions control for both radionuclide migration and ionizing radiation. Herein, a design methodology for georadiological (georad) barriers is developed on the basis of the principles of gamma (γ) radiation shielding and the practical ranges of barrier material characteristics. The intensities of gamma photons generated by parent and daughter radionuclides at the same energy level and time are summed up to derive total entry intensities for specific times ranging from 0 to 50 years, for various georad barrier thicknesses, dry densities, and volumetric moisture contents. A gamma reduction index (GRI) which ranges in magnitude from 0 to 1 in direct proportionality to γ attenuation, is developed and used to scale the effectiveness of barriers. The methodology is applied to 1.25 MeV energy gamma emissions from a site that is initially contaminated with Co-60 and Eu-154 at concentrations of 4.64× 10−11 and 9.0...

Bexarotene is a synthetic retinoid from the subclass of retinoids called rexinoids which selectively activate retinoid X receptors. It has activity in cutaneous T-cell lymphoma (CTCL) and has been approved by the European Medicines Agency since 1999 for treatment of the skin manifestations of advanced-stage (IIB-IVB) CTCL in adult patients refractory to at least one systemic treatment. In vivo bexarotene produces primary hypothyroidism which may be managed with thyroxine replacement. It also affects lipid metabolism, typically resulting in raised triglycerides, which requires prophylactic lipid-modification therapy. Effects on neutrophils, glucose and liver function may also occur. These side-effects are dose dependent and may be controlled with corrective therapy or dose adjustments. To produce a U.K. statement outlining a bexarotene dosing schedule and monitoring protocol to enable bexarotene prescribers to deliver bexarotene safely for optimal effect. Leaders from U.K. supraregional centres produced this consensus statement after a series of meetings and a review of the literature. The statement outlines a bexarotene dosing schedule and monitoring protocol. This gives instructions on monitoring and treating thyroid, lipid, liver, blood count, creatine kinase, glucose and amylase abnormalities. The statement also includes algorithms for a bexarotene protocol and lipid management, which may be used in the clinical setting. Clinical prescribing of bexarotene for patients with CTCL requires careful monitoring to allow safe administration of bexarotene at the optimal dose.

The association of child hyperactivity and parental psychopathology was explored by establishing lifetime DSM-III diagnoses and histories of childhood hyperactivity among the parents of boys, aged 7-11 yrs, in five diagnostic groups: attention deficit disorder with hyperactivity (ADDH), conduct disorder (CD), ADDH + CD, emotional disorder (ED) and no disorder (NC). These groups were differentiated by a family history of parental psychopathology or childhood hyperactivity. ADDH + CD, CD and ED groups all had significantly higher rates of parental psychopathology than the ADDH and NC groups, for which rates were similar. Significantly more boys in the ADDH, CD and ADDH + CD groups had family histories of parental childhood hyperactivity than did boys in the ED and NC groups.

Subjects with oppositional disorder (OD, N = 21) and conduct disorder (CD, N = 22) were compared with normal controls (NC, N = 20) to determine whether OD is a distinct disorder. OD subjects exhibited high rates of associated attention deficit, emotional and learning disorders. Compared with NC, OD subjects had high rates of problems in social relationships and came from families characterized by marital fights, dysfunction, and paternal psychopathology. Compared with CD, OD was less often characterized by undersocialization and separations from fathers and more often characterized by dissatisfaction in the marital relationship. These results suggest that OD is a variant of CD rather than of normality.

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Serum samples from 121 unrelated, healthy Japanese individuals were typed for several Gm and Km(1) allotypes. Peripheral blood lymphocytes from these subjects were cultured with streptococcal cell wall (SCW) antigen and the incorporation of 3H-thymidine into T lymphoblasts was measured. Log-linear analysis showed a significant interactive effect of Gm1,17;13,16,21 and Km(1) on the cellular immune response to group A SCW antigen.

Two experiments were conducted to determine whether hyperactive boys have a unique deficit in sustained attention. Groups with DSM-III diagnoses of attention deficit disorder (ADDH), conduct disorder (CD), ADDH + CD, and learning disorder were compared with normal controls on the Continuous Performance Task. In Experiment 1, stimulus presentation rate (stimulus onset asynchrony, SOA) and display time were varied to manipulate attentional demand, and speed and accuracy of performance were measured. The ADDH group was uniquely affected, with less accurate performance at the fastest and slowest SOA. To distinguish the effects of time on task and SOA, the duration of each SOA condition was held constant in Experiment 2. The poorer performance of the ADDH group at the fastest SOA was no longer evident. This finding indicates that the deficit of sustained attention in boys who have ADDH is associated with a greater susceptibility to refractory effects, which is influenced by practice.

The hypothesis that hyperactive children have a deficit in sustained attention was investigated. Eighteen children who had attention deficit disorder with hyperactivity (ADDH), aged 7 to 11 years, were compared with children who had conduct disorder (n = 15), mixed conduct disorder and ADDH (n = 26), emotional disorder (n = 18), or learning disability (n = 22), and with normal controls (n = 15). The subjects were tested on three versions of the Continuous Performance Task. Sustained attention was assessed from performance with increasing time on task and from ability to prepare attention in response to a warning. Performance of all subjects deteriorated with increasing time and improved with the opportunity to prepare attention. Hyperactive subjects were not more adversely affected by increasing time, nor did they benefit less than controls from the opportunity to prepare attention. Data reanalysis after rediagnosis according to ICD-9 criteria did not change the results. This study did not confirm the hypothesis that hyperactive children have a unique sustained attention deficit.

Maprotiline has been reported to be less likely to cause epileptic seizures than the tricyclic antidepressants. The authors describe two cases in which patients suffered their first epileptic attacks while on therapeutic doses of maprotiline. They recommend that the newer antidepressants, as well as the tricyclics, should not be used with the aliphatic neuroleptics because of a possible additive or synergistic epileptic effect. If patients are to be withdrawn from C.N.S. depressants, then this should be accomplished prior to initiation of antidepressant therapy. Patients who are predisposed to seizures should have lower initial doses of antidepressants.

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